Type 2 diabetes, also referred to as non-insulin dependent diabetes mellitus (NIDDM), afflicts between 80 and 90% of all diabetic patients in developed countries. In the United States alone, approximately 15 million people, and more than 100 million worldwide, are affected. Because this disorder is a late onset disease and occurs often in overweight persons it can be expected that the number of patients suffering from this disease will increase further. Patients suffering from type 2 diabetes usually still produce insulin but become increasingly resistant to their own insulin and to insulin therapy. A promising new class of drugs has been recently introduced that resensitizes patients to their own insulin (insulin sensitizers), thereby reducing the requirement for exogenous insulin. Troglitazone (Resulin™) and rosiglitazone (Avandia™) are among the first representatives of a class of drugs approved for the treatment of type 2 diabetes in the United States and several other countries. These drugs, however, have side effects including rare but severe liver toxicities (i.e., troglitazone) and they can increase body weight in humans. Such side effects are of major concern for patients who might require treatment for diabetes for a decade or longer. Therefore, new and better drugs for the treatment of type 2 diabetes and related disorders are needed.
One property of the compounds of this invention is that in many cases they can convert preadipocyte cells to adipocytes i.e. induce adipocyte differentiation. The ability of a molecule to induce differentiation of a particular cell type or cell types is also known to often correlate to anticancer activities.
Small molecules that can be effective for the treatment of diabetes and/or disorders of carbohydrate metabolism were disclosed in U.S. Pat. No. 6,515,003, issued Feb. 4, 2003, based on U.S. patent application Ser. No. 09/652,810, filed Aug. 31, 2000, which claimed priority to U.S. Provisional Patent Application No. 60/151,670, filed Aug. 31, 1999. Related small molecules that can be useful in the treatment of certain cancers were disclosed in PCT Patent Application WO 01/16122, published Mar. 8, 2001, which claimed priority to the same U.S. Provisional Patent Application No. 60/151,670 cited above. The disclosures of all the above-described patent documents are hereby incorporated herein by this reference, for both their chemical structural disclosures, their teachings of the biological activities of those compounds, and methods for their use as pharmaceutical compositions.
There is however a continuing need for new drugs for the treatment of type 2 diabetes and associated disorders of carbohydrate and/or lipid metabolism, including hyperlipidemia and hypercholesterolemia. In particular, new drugs that can control the blood sugar levels of diabetics, and simultaneously control hyperlipidemia and/or hypercholesteremia so as to lessen or prevent atherosclerosis would be of high value for the treatment of diabetes.